DESCRIPTION: (Verbatim from the Applicant's Abstract) The goal of this Phase I SBIR application is to develop a long acting injectable antidepressant for use in depressed, non-compliant HIV-seropositive individuals. HIV-seropositive individuals have increased rates of depression and medication non-compliance. We have developed a synthetic approach for substituting a decanoate moiety on the free amine of antidepressants resulting in a long acting compound. Sertraline has certain pharmacokinetic advantages over other antidepressants. The proposed studies will develop sertraline decanamide as a long acting antidepressant for parenteral administration. Our Specific Aims are: Specific Aim 1: Manufacture sufficient sertraline decanamide for proposed studies. Specific Aim 2: Determine the dose-response curves of sertraline decanamide (i.m. in oil) and sertraline HCI for inhibiting serotonin uptake by rat brain synaptosomes after in vivo administration. Specific Aim 3: Determine the selectivity of sertraline decanamide and sertraline HCI for inhibiting serotonin uptake in vitro. Concentration-response curves for the in vitro inhibition of synaptosomal norepinephrine, dopamine and serotonin uptake will be generated for the two compounds and compared. Specific Aim 4: Determine the long-term time course (0 to 28 days) for inhibition of synaptosomal serotonin uptake by sertraline decanamide (i.m. in oil) and sertraline HCI after a single dose. PROPOSED COMMERCIAL APPLICATION: Not Available